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- Title
Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers.
- Authors
Stein, Murray B.; Chia-Yen Chen; Ursano, Robert J.; Tianxi Cai; Gelernter, Joel; Heeringa, Steven G.; Jain, Sonia; Jensen, Kevin P.; Maihofer, Adam X.; Mitchell, Colter; Nievergelt, Caroline M.; Nock, Matthew K.; Neale, Benjamin M.; Polimanti, Renato; Ripke, Stephan; Xiaoying Sun; Thomas, Michael L.; Qian Wang; Ware, Erin B.; Borja, Susan
- Abstract
<bold>Importance: </bold>Posttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity.<bold>Objective: </bold>To discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).<bold>Design, Setting, and Participants: </bold>Two coordinated genome-wide association studies of mental health in the US military contributed participants. The New Soldier Study (NSS) included 3167 unique participants with PTSD and 4607 trauma-exposed control individuals; the Pre/Post Deployment Study (PPDS) included 947 unique participants with PTSD and 4969 trauma-exposed controls. The NSS data were collected from February 1, 2011, to November 30, 2012; the PDDS data, from January 9 to April 30, 2012. The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015.<bold>Main Outcomes and Measures: </bold>Association analyses for PTSD used logistic regression models within each of 3 ancestral groups (European, African, and Latino American) by study, followed by meta-analysis. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated.<bold>Results: </bold>The NSS population was 80.7% male (6277 of 7774 participants; mean [SD] age, 20.9 [3.3] years); the PPDS population, 94.4% male (5583 of 5916 participants; mean [SD] age, 26.5 [6.0] years). A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 × 10-8) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 × 10-8) in the African American samples from the NSS. A genome-wide significant locus was also found in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 × 10-8) in the European American samples from the NSS. Similar results were not found for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses. Single-nucleotide polymorphism-based heritability was nonsignificant, and no significant genetic correlations were observed between PTSD and 6 mental disorders or 9 immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis.<bold>Conclusions and Relevance: </bold>In the largest genome-wide association study of PTSD to date, involving a US military sample, limited evidence of association for specific loci was found. Further efforts are needed to replicate the genome-wide significant association with ANKRD55-associated in prior research with several autoimmune and inflammatory disorders-and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis.
- Subjects
POST-traumatic stress disorder; MENTAL health of military personnel; PSYCHOLOGY of military personnel; UNITED States. Army; PSYCHOLOGICAL resilience; SINGLE nucleotide polymorphisms; GENETICS; CARRIER proteins; CHROMOSOMES; DISEASE susceptibility; GENETIC polymorphisms; GENOMES; LONGITUDINAL method; META-analysis; RESEARCH funding; CASE-control method; SEQUENCE analysis
- Publication
JAMA Psychiatry, 2016, Vol 73, Issue 7, p695
- ISSN
2168-622X
- Publication type
journal article
- DOI
10.1001/jamapsychiatry.2016.0350